Autoinflammatory keratinization disease with hepatitis and autism reveals roles for JAK1 kinase hyperactivity in autoinflammation.

Clinical observations reinforced by analysis of a knock-in mouse model confirm the crucial role of JAK1 in regulating physiological inflammatory processes. The present findings expand the phenotypic spectrum resulted from JAK1 hyperactivation and further underscore how gain-of-function JAK1 mutations contribute to multisystem autoinflammation. RNA sequencing was performed using extracted RNA from the brain, liver, and skin of newborn Jak1 knock in (KI) mice (Jak1H595D/+;I596I/+;Y597Y/+) and wild type (WT) mice . We performed a gene set enrichment analysis using the hallmark gene set database.依托敲入小鼠模型（knock-in mouse model）的分析所佐证的临床观察结果，证实了JAK1在调控生理性炎症进程中的核心作用。本研究所得结果拓展了JAK1过度激活（JAK1 hyperactivation）所导致的表型谱，并进一步阐明了功能获得性JAK1突变（gain-of-function JAK1 mutations）如何介导多系统自身炎症性疾病的发生。本研究使用提取自新生Jak1敲入（knock-in, KI）小鼠（基因型为Jak1H595D/+;I596I/+;Y597Y/+）与野生型（wild type, WT）小鼠的脑、肝、皮肤组织RNA，开展了RNA测序（RNA sequencing）实验。研究团队采用标志性基因集数据库（hallmark gene set database）完成了基因集富集分析（gene set enrichment analysis）。